turning the tide on cancer...turning the tide on cancer february 2021 forward-looking statements...

Turning the Tide on CancerFebruary 2021

Forward-Looking StatementsCertain statements in this presentation are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. Thesestatements may be identified by the use of words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar terms orexpressions that concern our expectations, strategy, plans or intentions. These forward-looking statements are based on our current expectationsand actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated bysuch forward-looking statements. These factors include, but are not limited to, our need for additional financing; our ability to continue as a goingconcern; clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not bepredictive of future trial results; our clinical trials may be suspended or discontinued due to unexpected side effects or other safety risks that couldpreclude approval of our product candidates; risks related to business interruptions, including the outbreak of COVID-19 coronavirus, which couldseriously harm our financial condition and increase our costs and expenses; uncertainties of government or third party payer reimbursement;dependence on key personnel; limited experience in marketing and sales; substantial competition; uncertainties of patent protection and litigation;dependence upon third parties; our ability to develop tests, kits and systems and the success of those products; regulatory, financial and businessrisks related to our international expansion and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDAregulations. There are no guarantees that any of our technology or products will be utilized or prove to be commercially successful. Additionally,there are no guarantees that future clinical trials will be completed or successful or that any precision medicine therapeutics will receive regulatoryapproval for any indication or prove to be commercially successful. Investors should read the risk factors set forth in our Form 10-K for the yearended December 31, 2019, and other periodic reports filed with the Securities and Exchange Commission. While the list of factors presented hereis considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factorsmay present significant additional obstacles to the realization of forward-looking statements. Forward-looking statements included herein aremade as of the date hereof, and we do not undertake any obligation to update publicly such statements to reflect subsequent events orcircumstances.

2020 Corporation Presentation I 3

Investment Highlights

PLK: Polo-like Kinase; SOC: Standard-of-care; ORR: Overall response rate; MOA: Mechanism of action; mCRC: metastatic colorectal cancer; mCRPC: metastatic castration resistant prostate cancer; PDAC: Pancreatic ductal adenocarcinoma; AML: Acute myeloid leukemia

Clinical data from ongoing trialssupport the use of onvansertib in combination regimens across Numerous aggressive cancers:• mCRC Phase 1b/2 trial• mCRPC Phase 2 trial• PDAC Phase 2 trial• AML Phase 2 trial

Expansion opportunities:• Chronic myelomonocytic leukemia• Triple negative breast cancer• Lung cancer• Ovarian cancer

Diversified Pipeline Across Numerous Cancers

Circulating Tumor DNA: changes in KRAS mutational burden in blood are predictive of subsequent tumor shrinkage (mCRC)

Circulating Tumor Cells: changes are predictive of overcoming anti-androgen resistance (mCRPC)

Circulating Tumor DNA: changes arepredictive of decreases in leukemic bone marrow cells (AML)

Integrated Biomarker Strategy

Supported by compelling preliminary clinical data from a Phase 1b/2 trial showing a ten-fold improvement in ORR compared to SOC

Preclinical data support:• MOA of synthetic lethality between

KRAS mutant mCRC and PLK1 inhibition

• Synergy with irinotecan and 5-FU

First Indication: 2nd line treatment in patients who have failed 1st line treatment with FOLFOX with/without bevacizumab

FDA Fast Track Designation

Strong Lead Program in KRAS-mutated mCRC

Onvansertib overcomes the shortcomings of prior PLK inhibitors:

• Highly selective for PLK1• Orally administered• 24-hour half-life • Flexible dose and schedule

Specifically targets a known mechanism of cell division that is required for tumor cell viability

Preliminary clinical data demonstrate the safety, tolerability and efficacy of onvansertib in combination with SOC across multiple indications

3rd Generation, 1st-in-class, Oral PLK1 Inhibitor


Experienced Management Team With Drug Development and Biomarker Technology Expertise

Mark Erlander, PhDChief Executive Officer

Vicki KelemenChief Operating Officer

Brigitte LindsayVice President of Finance

Onvansertib

3rd generation, 1st in class, oral and highly selective PLK1 inhibitor addressing unmet needs across a broad range of cancer indications


PLK1 is a Proven Therapeutic Target that is Overexpressed in Most Cancers

• PLK1 is a serine/threonine kinase and master regulator of cell-cycle progression

• PLK1 controls G2/mitosis (G2/M) checkpoint

• Inhibition of PLK1 causes mitotic arrest and subsequent cell death

• Emerging data demonstrate that PLK1 is also a key regulator of cellular functions beyond mitosis that are essential for tumor growth:

- Biosynthesis of DNA

- DNA Damage Response

1Zitouni et al., Nat Rev Mol Cell Biol. 2014 Jul;15(7):433-52; PLK1: Polo-like kinase 1

Inhibition of PLK1 causes mitotic arrest and subsequent cell death1


PLK1-Specific ATP Competitive Inhibitor1

1Valsasina Mol Cancer Ther 2012

Enzyme IC50 (μM)

PLK1 0.002

PLK2PLK3

CK2FLT3CDK1/CycB

42 additional kinases in house

>190 additional kinases in the Millipore panel

>10>10

0.40.43.8

>10

>10

Biochemical Profile

Small Molecule MW 648.60 Daltons

Formulation 5mg and 20mg oral gelcaps

Plasma Protein Binding 95% at 10μM and 91% at 50μM

Metabolic Overview

Moderate intrinsic clearance (9.3 mL/min/kg)1

2 metabolites identified in metabolic profiling in low quantities (parent drug accounted for 93% of total drug-related material)1

No Cytochrome P450 inhibition at therapeutic concentrations2

Pharmacokinetics3

Systemic exposure of drug increased with dose, as shown by an increase in Cmax and AUC0-24

Tmax is approximatively 3h

Half-life is approximately 24h

Profile Characteristics Co-crystal of Onvansertib with PLK1

• A selective, ATP competitive PLK1 inhibitor• Selectivity is driven by polar interaction with the side chain of Glu140 of PLK1• Interaction is hampered in both PLK2 and PLK3 where Glu140 is replaced by histidine

Onvansertib

Substituted by His in PLK2 and PLK3


Optimal Drug Properties

Onvansertib has Optimal Drug Properties and Synergistically Combines with Standard-of-Care Therapies

Zytiga®

(abiraterone)

Avastin®

(bevacizumab)Taxol®

(paclitaxel)

Venclexta®

(venetoclax) Cytarabine

DoxorubicinCamptosar®

(irinotecan)

Beleodaq®

(belinostat)

Cisplatin

Gemzar®

(gemcitabine)

5-FU

Velcade®

(bortezomib)

Onvansertib

High SelectivityFor PLK1

DemonstratedSafety and Tolerability

Synergistic in Combination

Flexible Dosingand Scheduling

PredictiveBiomarker

Oral Administration

IdealPharmacokinetics

24-hourHalf-life

Onvansertib

Synergistic in Combination with Standard-of-Care Chemo and Targeted Therapies

Second-Line Treatment of KRAS-Mutated mCRC Phase 1b/2 open-label trial of onvansertib + FOLFIRI/bevacizumabTrial Sites: USC Norris Comprehensive Cancer Center; Mayo Clinics (Arizona, Minnesota, Florida), Kansas University Medical Center, CARTI Cancer Center, Inova Schar Cancer InstitutePrincipal Investigator: Dr. Heinz-Josef Lenz


New Second-Line Therapies are Needed to Improve Response and Increase Progression-Free Survival

1Kubicka et al, Annals of Oncology 2013; 2342–2349; mCRC: Metastatic colorectal cancer

Significant limitations to standard-of-care (SOC)

Historically, second-line standard-of-care treatment in KRAS-mutated mCRC has had an overall response rate of 4% and progression-free survival (PFS) of 5.5 months1

50% of patients with mCRC have a KRAS mutation

Prognosis is poor with a five-year survival rate of 10%

Other drugs currently in development do not address the most prevalent

KRAS mutations in mCRC

4% Response

to SOC

5.5Months

PFS


KRAS is a Pivotal Diagnostic Biomarker in the CRC Treatment Paradigm

• KRAS-mutated patients do not benefit from anti-EGFR agents:

– No increase in OS, PFS and ORR was observed in KRAS mutant patients treated with EGFR inhibitors vs control arm1,2

– The use of anti-EGFRs is therefore limited to KRAS wild-type patients

• Mutations in KRAS represent also the most frequent mechanism of resistance to anti-EGFRs (i.e. cetuximab)

1Karapetis et al., NEJM 2008;359:1757-1765; 2Amado et al., JCO 2008, 26:1626-1634

KRAS Wild-type

mCRC

KRAS Wild Type

Chemotherapy + EGFR inhibitor

Chemotherapy ±bevacizumab

KRAS Mutant

Treatment ParadigmKRAS MutantKRAS Mutant


Second-line Treatment: Real World Utilization in the US

Flatiron Health Data

Source: Hess, L. International Journal of Colorectal Disease; 2019. Data is limited to limited to second-line regimens used in >1% of the cohort. FOLFOX: fluoropyrimidine, leucovorin, oxaliplatin. FOLFIRI: fluoropyrimidine, leucovorin, irinotecan, FOLFOXIRI: fluoropyrimidine, leucovorin, irinotecan, oxaliplatin

255 Cancer clinics representing

1.7 million active cancer patients

14,315Colorectal cancer patients

7,034Colorectal cancer patients who

receive second line therapyDenotes combination with bevacizumab

Denotes combination with other antiangiogenics


FDA Approved Standard-of-Care, FOLFIRI + Bev, has an ORR Rate of 5% and PFS of 5.7 months in Pivotal Trial Used for Registration

Outcomes for patients in the 2nd line setting is poor• Addition of bevacizumab to FOLFIRI improves outcomes1

• While KRAS WT patients benefit from the addition of bevacizumab, there was no statistically significant improvement in OS forKRAS-mutant patients2

• KRAS-mutant patients have lower ORR, PFS and OS2

• The anti-angiogenic agents aflibercept and ramucirumab, although used to a lesser extent, have an ORR of 11.8 – 13.4%3-4

1Bennouna et al., Lancet Oncol. 2013; 14(1):29-37; 2Kubicka, S, Annals of Oncology 2013, 24:2342-2349; CI: confidence interval, HR: hazard ration, ORR: objective response rate, PFS: progression-free survival, OS: overall survival, WT: wild-type, MUT: mutant; 3Van Cutsem et al., Target Oncology 2016, 11:383-400 4Tabernero et al., Lancet Oncology 2015;16:499-508

KRAS Treatment ORR PFS (months)

HR and significance of PFS

OS (months)

HR and significance of OS

All Patients2

FOLFIRI 3% 4.1 HR=0.68(95 % CI 0.59-0.78)

P <0.0001

9.8 HR=0.81(95 % CI 0.69-0.94)

P <0.0062FOLFIRI + Bev 5% 5.7 11.2

KRAS WT2

FOLFIRI 5% 4.5 HR=0.61 (95 % CI 0.49-0.77)

P <0.0001

11.1 HR=0.61 (95 % CI 0.53-0.90)

P=0.0052FOLFIRI + Bev 7% 6.4 15.4

KRAS MUTANT2

FOLFIRI 3% 4.1 HR=0.70 (95 % CI 0.56-0.89)

P = 0.0027

10 HR=0.92 (95 % CI 0.71-1.18)

P=0.4969FOLFIRI + Bev 4% 5.5 10.4


Synthetic Lethality: Cells with KRAS Mutations are Hypersensitive to Inhibition of PLK1

The output of the RAS-mutated pathway activates PLK1, which is inhibited by onvansertib

PLK1: Polo-like Kinase 1; mCRC: Metastatic colorectal cancer

Onvansertib Addresses KRAS Mutation Subtypes in mCRC

39%

22%

18%

8%6%

6%

2% 1%

G12D G12V G13D G12C G12S G12A Q61H G12R

Cell Viability in Onvansertib-Treated KRAS Mutant and Wild Type Isogenic CRC Cells


RAS activates PLK1 through a MEK/ERK-independent mechanism

PLK1 and RAS Cooperative Relationship

1Mielgo et al., Nat. Med. 2011; 17(12):1641-5

The downstream target of KRAS, pCRAF, localizes to the mitotic spindle poles at mitosis where it interacts with PLK1 and promotes PLK1 activation, leading to mitosis and tumor progression1

Data suggest that KRAS-activated cells are dependent on PLK1 for their proliferation and survival and inhibition of PLK1 by onvansertib could inhibit tumor growth

RAS

RAF

P

CRAF

P

PLK1

PLK1 Activity

Mitotic Progression

MEKP

ERKP

Proliferation/Survival

Onvansertib


Synergy in Combination with Irinotecan Synergy in Combination with 5-FU

Onvansertib works synergistically in combination with standard-of-care FOLFIRI (irinotecan and 5-FU) HCT-116 (with G13D KRAS mutation)

Synergy: Onvansertib in Combination with SOC Irinotecan and 5-FU


PLK1 Regulates DNA Damage Response1,2

1van Vugt & Yaffe, Cell Cycle 2010 9:2097-2101; 2van Vugt et al., 2010, PLoS 8:1-19

DNA Damaging Agents

• Irinotecan• 5-FU

G2/M Arrest

DNA Damage Response

(DDR) arrests cells at G2/M checkpoint

Mitosis

1. Checkpoint adaptation 2. PLK1 inhibits DDR, induces

mitotic entry for tumor cells & cell division

Cell Death

1. Keeps tumor cells in G2/M arrest leading to apoptosis

2. For cells that escape, mitosis is blocked, also leading to apoptosis


Phase 1b/2 Open Label Trial of Onvansertib + FOLFIRI/bevacizumab

Trial Design

Efficacy Endpoints• Overall response rate (ORR) in patients who receive ≥1 cycle (2

courses) of treatment• Progression-free survival (PFS) • Decreases in KRAS mutation burden and response to treatment

1 CYCLE = 28 Days

Treatment Course = 14 Days Treatment Course = 14 Days

2 3 4 5 6 - 141 2 3 4 5 6 - 141

Onvansertib Onvansertib

FOLFIRI + bevacizumab FOLFIRI + bevacizumab

• ≥5 of 26 (~20%) patients achieve clinical response confirmed by radiographic scan

• Achieve median progression-free survival of ≥ 6 months

What is Clinical Trial Success


Phase 1b Enrollment and Patient Baseline Characteristics

Dose Escalation Patient Cohorts(as of 06-Jan-2021)

Number of patients (N)

Dose Level 0Onvansertib

12 mg/m2

Dose Level +1Onvansertib

15 mg/m2

Dose level +2Onvansertib

18 mg/m2

Completed Cycle 1 5 6 5

Currently on Treatment 0 3 2

• Phase 1b: 3+3 dose escalation design to assess the safety of the combination and identify the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of onvansertib

Total patients N=18 Median [range] or n (%)Age (years) 59 [37-83]SexMale 8 (44%)Female 10 (56%)

ECOG0 8 (44%)1 10 (56%)

Primary tumor siteColon 9 (50%)Rectum 7 (39%)Unknown 2 (11%)

Liver metastasisNone 7 (39%)Liver and other 8 (44%)Liver only 2 (17%)

Number of metastatic organs1 7 (39%)≥2 11 (61%)

Prior Bevacizumab treatmentYes 13 (72%)No 5 (28%)


Phase 1b Safety Assessment

• 5 patients had G4 adverse events: – 1 patient had a G4 neutropenic fever at dose level 12 mg/m2

– 1 patient had a G4 neutropenia at dose level 15 mg/m2

– 3 patients had a G4 neutropenia dose level 18 mg/m2

• The onvansertib RP2D was confirmed at 15 mg/m2

• The combination regimen was well tolerated:– Of all AEs only 8% (17/202) were G3/G4– The only G3/G4 AE reported in ≥2 patients were

neutropenia (n=8); which was managed by dose delay, growth factor and/or discontinuation of the 5-FU bolus; no patients went off trial due to neutropenia

• No major or unexpected toxicities were attributed to onvansertib

Adverse Events (AEs) Grade 1

Grade 2

Grade 3

Grade 4

All Grades

Fatigue 4 7 1 0 12Nausea 8 3 1 0 12Neutropenia 1 2 4 4 11Diarrhoea 7 2 0 0 9Alopecia 6 1 0 0 7Abdominal pain 1 4 1 0 6Anaemia 4 1 0 0 5WBC decrease 2 3 0 0 5Vomiting 3 1 1 0 5Stomatitis 4 1 0 0 5Thrombocytopenia 2 2 0 0 4Mucosal inflammation 1 2 0 0 3Dyspepsia 3 0 0 0 3ALT increased 2 1 0 0 3Abdominal distension 3 0 0 0 3Back pain 3 0 0 0 3Epistaxis 3 0 0 0 3

n=number of patients (total N=18); WBC=white blood cells; ALT= alanine aminotransferase

Most Common Treatment-Emergent AEs


Phase 1b Preliminary Efficacy

• 18 patients were treated in Phase 1b (6 patients at each dose level); 2 patients did not complete cycle 1 (1 at 12 mg/m2 and 1 at 18 mg/m2); 2 patients at 15 mg/m2 completed cycle 1 of treatment, but have not reached their first 8-week scan

• 14 patients are currently evaluable for efficacy*:– 12 of 14 (86%) patients achieved a clinical benefit (SD + PR)– 5 (36%) patients have achieved a partial response (PR); 4 patients had a confirmed PR; 1 patient went on to have curative surgery; 1

patient with non-confirmed PR went off study following PR due to treatment-unrelated AE– Time to patients on trial achieving a PR ranges from 2 to 6 months

*completed at least 1 cycle of treatment and had radiographic scan or progressed within 8 weeks while on treatment

Treatment Response and Duration(as of 06-Jan-2021)

Baseli

ne

8 wee

ks

16 w

eeks

24 w

eeks

32 w

eeks

40 w

eeks

48 w

eeks

56 w

eeks

64 w

eeks

-60

-40

-20

0

20

40

60

80

100

% c

hang

e in

targ

etle

sion

s fro

m b

asel

ine

01-00302-00402-00501-00601-00702-00801-01001-01102-01201-01301-014

SD

PD

PR

02-016

Changes in Tumor Size From Baseline

0 28 56 84 112

140

168

196

224

252

280

308

336

364

392

420

448

476

02-01501-01402-01601-01302-012

02-00801-01901-01101-010

02-00502-00401-00301-00601-007

⊗

⊗

→

→

→

Days of treatment

8 weeks16 weeks

24 weeks

32 weeks

Radiographic assessment

Partial Response (PR)

Stable Disease (SD)

Progressive Disease (PD)

12 m

g/m

215

mg/

m2

18 m

g/m

2

40 weeks

48 weeks Treatment ongoing→

Curative surgery

Patient/MD decision

Reason for discontinuation

Treatment-unrelated AE⊗

56 weeks

Received bevacizumab in 1st line

Dose level +1Dose level -1

Onvansertib dose adjustments

64 weeks


KRAS Mutant Allelic Frequency (MAF) Biomarker Analyses

• KRAS MAF was measured by digital droplet PCR (ddPCR) at baseline (Cycle 1 Day 1, pre-dose) and on-treatment (Day 1 of Cycles 2 to 9)

• 12 of 14 patients had a KRAS mutation detected by ddPCR at baseline (all had a KRAS mutation detected by NGS)

• Clinical responses were observed across different KRAS mutations, including the 3 most common in CRC (G12D, G12V, G13D)

• The greatest decreases in KRAS MAF after 1 cycle of treatment were observed in patients achieving a PR

– All 5 patients with a PR had >75% decrease– 4 of the 5 patients with SD had reductions >75%– the 2 patients who progressed showed a more modest

decrease in KRAS MAF (-55% and -26%)

PR: partial response, SD: stable disease, PD: progressive disease; CXD1: Cycle X Day 1

% KRAS MAF Decrease Following 1 Cycle of Treatment

02-00

4

01-01

0

02-00

5

01-00

7

01-01

3

02-01

6

01-01

9

02-01

2

01-01

1

01-00

6

02-00

8

02-01

5

-100

-50

0

% c

hang

e in

KR

AS M

AF a

tC

ycle

2 D

ay 1

from

bas

elin

e

PR SD PD

75% decrease


Conclusions

• Safety Assessment:– The combination of onvansertib and FOLFIRI/Bev is well-tolerated

– Onvansertib RP2D was established at 15 mg/m2

• Preliminary Efficacy:– 12 of 14 (86%) patients evaluable for efficacy achieved a clinical benefit (SD + PR)

– 5 (36%) patients achieved a partial response (PR), including 4 confirmed PRs; 1 patient proceeded to curative surgery

• KRAS Mutant Allelic Frequency (MAF) Biomarker:– Clinical responses were observed across different KRAS variants, including the 3 most common in CRC– Patients achieving a PR or SD showed the greatest decreases in plasma mutant KRAS after one cycle of therapy

• Phase 2 Currently Enrolling at 7 trial sites: – Further assess the safety and efficacy of onvansertib at the RP2D in combination with FOLFIRI + bevacizumab

– Evaluate the value of KRAS liquid biopsy to predict treatment response


Catalysts and Milestones: KRAS-Mutated mCRC

mCRC: Metastatic colorectal cancer

May 2020: Fast Track Designation Granted by FDA

January 2021: ASCO-GI virtual poster presentation

Q2 2021: FDA End of Phase (EOP1b) meeting – potential path to approval discussion

Fast Track Designation enables more frequent interaction with the FDA and facilitates an accelerated clinical development pathway

ESMO 2021: ESMO mCRC Phase 2 Data

Second-Line Treatment of Metastatic PDACPhase 2 open label trial of onvansertib + nanoliposomal irinotecan, 5-FU and leucovorinTrial Sites: Mayo Clinics (Arizona, Minnesota, Florida), Emory University, Kansas University Medical Center and Inova Schar Cancer InstitutePrincipal Investigator: Dr. Daniel H. Ahn


The promising response rates and impressive durability seen in KRAS-mutated mCRC with the combination of onvansertib + irinotecan + 5-FU, support onvansertib’s potential in PDAC, where ~95% of patients have a KRAS mutation

Leveraging the synergy between onvansertib and irinotecan + 5-FU

New Second-Line Therapies are Needed for Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) Patients

Second-line treatment with SOC irinotecan + 5-FU/leucovorin offers a mOS benefit of only 6.1 months2

Mutant KRAS contributes to treatment resistance and metastases

and is essential for PDAC growth3

3.1Months

PFS

Response to SOC

7.7%

Second-line treatment with SOC irinotecan + 5-FU/leucovorin has a

response rate of only 7.7%1

1Onyvide Package Insert: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207793lbl.pdf; 2Wang-Gillam A, Li C-P, Bodoky G, et al. Lancet 2016;387:545-57. 3Waters AM, Der CJ. Cold Spring Harb Perspect Med 2018;8(9). SOC: Standard-of-care; PFS: Progression free survival

https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207793lbl.pdf


Phase 2 Open Label Trial of Onvansertib + Nanoliposomal Irinotecan + 5-FU in Metastatic PDAC

Trial Design (~45 patients):

Eligibility Criteria• Prior abraxane/gemcitabine and no prior irinotecan, nanoliposomal

irinotecan or investigational PLK1 inhibitorPrimary Efficacy Endpoint• Overall response rate (ORR)

1 CYCLE = 14 Days

Treatment Course (Days)

5-FU + Nanoliposomal Irinotecan (nal-IRI)

• 8 of 39 (≥20%) patients achieve ORR


3 5 7 9 11 - 141 8642 10

Onvansertib 12 mg/m2

Onvansertib to be administered on Days 1-10 (12 mg/m2) based on safety lead-in of 6 patients (with option to dose 15 mg/m2 on Days 1-5)


January 2021: Received FDA “Study May Proceed”

January 2022: ASCO-GI Phase 2 data presentation

April 2022: AACR biomarker data presentation

September 2022: ESMO Phase 2 data presentation

Projected Catalysts and Milestones: Metastatic PDAC

Metastatic Castration-Resistant Prostate CancerPhase 2 open-label trial of onvansertib + abiraterone Trial Sites: Beth Israel Deaconess, Dana Farber, Mass General HospitalPrincipal Investigator: Dr. David Einstein


New Therapeutic Options are Needed to Overcome Resistance to SOC Androgen Receptor Signaling Inhibitors (ARSi)

1Antonarakis, Emmannel – Current Understanding of Resistance to Abiraterone and Enzalutamide in Advanced Prostate Cancer; Clinical Advances in Hematology & Oncology – May 2016 – Volume 14, Issue 5; 2Armstrong et al., 2019, JCO 37: 1120-1129; SOC: Standard-of-care; mCRPC: Metastatic castration resistant prostate cancer

Resistance develops to treatment with standard of care ARSi’s within 9-15 months1

ARSi’s offer a median overall survival (mOS) benefit of only ~4 months1

No effective treatment options are available for the up to 40% of mCRPC

patients with an AR-V7 mutation2

Limited options for patients once resistant to abiraterone

New treatment options are needed to extend the duration of response to ARSi’s and increase overall survival

9-15Months until

ARSi resistance

~4Month mOS

benefit

2020 Corporation Presentation I 311Patterson & Yaffe, 2019, MIT; mCRPC: Metastatic castration resistant prostate cancer

Onvansertib + Abiraterone (Zytiga®) Demonstrate Synergy in mCRPC model (C4-2)1

Onvansertib + Abiraterone (Zytiga®) Significantly Increase Mitotic Arrest1

Onvansertib works synergistically in combination with abiraterone (Zytiga®) and significantly increases mitotic arrest

Onvansertib Extends the Response to Androgen Receptor Signaling Inhibitors


Phase 2 Open Label Trial in of Onvansertib + Abiraterone

Note: radiographic assessment by RECIST v1.1 [CR = disappearance of all target lesions, PR = ≥30% decrease, PD = ≥20% increase, SD = does not meet criteria for PR nor PD]; mCRPC: Metastatic castration resistant prostate cancer; PSA: Prostate specific antigen; PFS: Progression-free survival

Trial Design:

Eligibility CriteriaInitial resistance to Zytiga; 2 consecutive rises in PSA levels

Efficacy Endpoint: Internationally Recognized Prostate Cancer Working Group

• Primary: disease control evaluated as PSA decline or stabilization (PSA rise <25% over baseline)

Dosing Schedule Duration Efficacy Endpoint

Cohort A (n = 24) Cohort Closed

Onvansertib 24mg/m2 Days 1-5 (21-day cycle) + Zytiga® (Abiraterone) 4 Cycles = 12 WeeksDisease Control (PSA Stabilization or Decline)

Cohort B (n = 32) Onvansertib 18mg/m2 Days 1-5 (14-day cycle) + Zytiga® (Abiraterone) 6 Cycles = 12 WeeksDisease Control (PSA Stabilization or Decline)

Cohort C (n = 32) Onvansertib 12mg/m2 Days 1-14 (21-day cycle) + Zytiga® (Abiraterone) 4 Cycles = 12 WeeksDisease Control (PSA Stabilization or Decline)

• ~30% patients achieve primary efficacy endpoint of disease control at 12 weeks (PSA stabilization or decrease); confirmed by radiographic scan

• Achieve median radiographic PFS of ≥6 months


Disease Control Assessed by PSA Stabilization


Patient Baseline Characteristics and Enrollment Status

Total patients N=39 Median [range] or n (%)

Age in Years 72 [54-87]Nonwhite Ethnicity 5 (13%)ECOG

01

34 (87%)5 (13%)

Years Since Diagnosis 5 [1-18]Grade Groups 4 and 5 24 (62%)De Novo Metastatic Disease 13 (33%)Presence of Bone Metastasis 33 (85%)Presence of Visceral Metastasis 13 (33%)Baseline PSA, ng/mL 12.5 [0.6-224]AR-V7+ at Baseline* 9 (23%)

Baseline CTC Count per mL of blood** 2.2 [0-87]

Patient Baseline Characteristics

ECOG: Eastern Cooperative Oncology Group, AR-V7: androgen receptor variant 7, CTC: circulating tumor cells*AR-V7 status was evaluated using the EPIC and Johns Hopkins University testing platforms **CTC count was performed by EPIC

Number of patients (N) Arm A Arm B Arm C

Treated 24 11 4

Currently on Treatment 1 1 4

Completing 12-weeks 14 8 3

Discontinued before 12 weeks

Progressive Disease (PD)Adverse EventWithdrew Consent

10 2 0

352

110

000

Patients evaluable for efficacy (completed 12 weeks + PD) 17 9 3

Enrollment as of October 16th, 2020


Phase 2 Data Demonstrate the Safety and Efficacy of Onvansertib in mCRPC

Adverse eventsTotal Patients N=39 Grade 1 Grade 2 Grade 3 Grade 4 All grades

Anemia 10 5 1 16

Thrombocytopenia 11 1 1 13

Fatigue 10 2 12

Neutropenia 1 1 7 3 12

Hypophosphatemia 3 3 4 10

WBC decrease 2 2 3 2 9

Back pain 2 3 5

Hypokalemia 3 1 1 5

Constipation 4 0 4

Nausea 3 1 4

• Most frequent Grade 3 and 4 adverse events (AEs) were expected, on-target, hematological associated with onvansertib mechanism of action

• Hematological AEs were reversible and effectively managed by dose delay, dose reduction and/or growth factor support

Safety Assessment

2020 Corporation Presentation I 352020 Corporation Presentation I

Phase 2 Data Demonstrate the Efficacy of Onvansertib and and Durability of Response Including Patients with AR Alterations

35

Treatment Response and Duration for Patients Completing 12 Weeks of Treatment

010

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Days of treatment

Progressive diseaseStable diseasePartial response

Radiographicassessment

AR-V7+AR T878A AR alterations

Transitioned to Arm B

3 months

6 months

9 months

1 year

Arm

B (5

+9)

Arm

A (5

+16)

1.5 year

Physcian decisionPatient decisionAdverse event*

Reason fordiscontinuationother than PD

AR Amplification

PSA endpoint

Ongoing→

Arm

C (1

4+7)

Total Patients Evaluable N=29 Arm A Arm B Arm C

Evaluable for efficacy* 17 10 4

Completed 12-week treatment 14 8 4

Progressed within 12 weeks 3 2 0

Disease control** 5 (29%) 3 (30%) 3 (75%)

Radiographic stable disease 9 (53%) 5 (50%) 4 (100%)

Durable response (>7 months) 4 (23%) 4 (40%) NA

* Completed 12 weeks of treatment or progressed within 12 weeks** Defined as PSA stabilization or decline (PSA rise <25% over baseline)

Efficacy Evaluation at 12-Weeks

Efficacy in patients with AR alterations:• 8 of the patients evaluable for efficacy had at least 1 AR

alterations: AR-V7+ (n=6), AR T878A mutation (n=2) and/or AR amplification (n=3)

• 3 (37%) patients achieved disease control • 4 (50%) patients had radiographic stable disease• 3 patients had durable responses (range 7-9 months)

*AR-V7 status was evaluated using the EPIC and Johns Hopkins University testing platforms. Genomic profiling of circulating tumor DNA was performed using Gardant360® test


Onvansertib-Induced Circulating Tumor Cell Decrease is Associated with Progression-Free Survival

At baseline, 27 (73%) of 37 patients had unfavorable CTC count; 10 were analyzed following 12 weeks of treatment:• 5 (50%) patients had an ≥80% CTC decrease, including 2

AR-V7+ patients (01-024 and 01-025)• 4 (40%) patients converted from unfavorable to favorable

CTC level, including 3 patients with no detectable CTC• Median time on treatment was 9.2 months for patients with

CTC decrease (n=5) vs 4.9 months for patients with CTC increase (n=5)

CRPC: Castration resistant prostate cancer

Circulating tumor cell (CTC) count, reported as favorable or unfavorable (<5 versus ≥5 CTC/7.5mL of blood, respectively) is aprognostic factor for survival in CRPC – conversion from unfavorable to favorable is associated with improved survival

Percent Change in CTC: 12-Weeks vs Baseline in Patients with Unfavorable CTC Level at Baseline


Identifying an Onvansertib-Abiraterone Response Gene Signature

Onvansertib/Abiraterone

Abiraterone induces expression of mitotic genes in prostate cancer

cells synergistic for Onv+Abi

• Synergy study• RNA-sequencing

Transcriptome analysis of 32,000 prostate cancer specimens

Identified 4 molecular subtypes:• Luminal A• Luminal Proliferating• Basal• Basal Immune

Currently analyzing archived tissue from patients enrolled

in the trialTranscriptome analysis with

Decipher Biosciences

Identification of anAbi/Onv synergy gene signature

Abi/Onv synergy gene signature is enriched in the Basal subtype, a subtype representing ~30% of CRPC patients and

associated with lower response to androgen deprivation therapy (ADT)

Correlate clinical response with Basal molecular subtype


Catalysts and Milestones: mCRPC

October 2020: Prostate Cancer Foundation (PCF)

February 2021: ASCO-GU presentation

April 2021: AACR Biomarker data presentation

October 2021: Prostate Cancer Foundation (PCF)

New Clinical Programs PlannedChronic Myelomonocytic Leukemia (CMML)


Study Rationale

• Proliferative CMML is enriched for activating RAS pathway mutations such as NRAS, KRAS, CBL, PTPN11 and NF1, all of which have been associated with adverse outcomes

• RAS pathway mutations drive proliferative CMML via a novel RAS-KMT2A-PLK1 axis, which can be therapeutically targeted with PLK1 inhibitors

• In-vitro and in-vivo experiments with onvansertib as a single agent have shown a dose-dependent inhibition of CMML cell growth, with improved cell differentiation

Activating RAS Pathway Can Be Therapeutically Targeted with PLK1 Inhibitors

PLK1

Phase 2 Study to Evaluate the Safety and Efficacy of Onvansertib in RAS-Pathway Mutant CMML

2020 Corporation Presentation I 412020 Corporation Presentation I 41

Phase 2 Two-Arm Randomized Trial of Onvansertib +/- Decitabine in RAS-Pathway Mutated CMML

Trial Design:

Eligibility Criteria:• Newly diagnosed or relapsed/refractory to prior therapy• RAS pathway mutant: NRAS, KRAS, PTPN11, CBL and NF1

with frequency allele of ≥5%

Efficacy Endpoint:• Rate of complete remission (CR)

Dosing Schedule Duration Efficacy Endpoint

Two Arms:Arm A (n=32) Treatment NaïveArm B (n=32) Relapsed/Refractory

Onvansertib 15 mg/m2 Days 1-14 (21-day cycle)

3 cycles monotherapy (option to add decitabine at cycle 4 if lack of efficacy with single agent)

Interim analysis of first 18 patients after 3 cycles to evaluate objective response

• Achieve ≥25% CR rate in treatment naïve cohort

• Achieve ≥12.5% CR rate in the relapsed and refractory cohort


Determine the safety and efficacy of onvansertib, a novel oral PLK1 inhibitor in RAS-pathway mutant chronic myelomonocytic leukemia

Corporate


Strong Patent Portfolio

PLK: Polo-like kinase; PSA: Prostate specific antigen

Evergreening: Biomarkers

Method for assessing PLK1 target phosphorylation status for identifying patients to be treated with PLK1 inhibitors

PCT US1948044, Expiration 2039

Method for treating patient with a PLK inhibitor when there is a PSA rise

Provisional, Expiration 2040

Evergreening: Combination Therapy

Exclusive license from MIT for 2 US issued patents with broad method claims for combination of PLK inhibitor + anti-androgen compounds to treat any cancer

US 9566280; US 10155006; Expiration 2035

Core Technology: 3 Issued Patents to 2030 in US, Europe and Asia, with anticipated extension to 2035

Compound (onvansertib): US 8614220

Salt forms of onvansertib: US 8648078

Combinations with anti-neoplastic compounds: US 8927530


Cardiff Oncology At-A-Glance

Clinical-stage biotech company, developing onvansertib, an oral, highly-selective Polo-like Kinase 1 (PLK1) inhibitor, to treat cancers

with the greatest medical need for new effective therapies

Exchange Nasdaq: CRDF

Cash & Cash Equivalents (as of 10/31/20) $131.8M

Q1 – Q3, 2020 Average Quarterly Cash Burn $3.8M

Headquarters San Diego, CA


Investment Highlights

PLK: Polo-like Kinase; SOC: Standard-of-care; ORR: Overall response rate; MOA: Mechanism of action; mCRC: metastatic colorectal cancer; mCRPC: metastatic castration resistant prostate cancer; PDAC: Pancreatic ductal adenocarcinoma; AML: Acute myeloid leukemia

Clinical data from ongoing trialssupport the use of onvansertib in combination regimens across numerous aggressive cancers:• mCRC Phase 1b/2 trial• mCRPC Phase 2 trial• PDAC Phase 2 trial• AML Phase 2 trial

Expansion opportunities:• Chronic myelomonocytic leukemia• Triple negative breast cancer• Lung cancer• Ovarian cancer

Diversified Pipeline Across Numerous Cancers

Circulating Tumor DNA: changes in KRAS mutational burden in blood are predictive of subsequent tumor shrinkage (mCRC)

Circulating Tumor Cells: changes are predictive of overcoming anti-androgen resistance (mCRPC)

Circulating Tumor DNA: changes arepredictive of decreases in leukemic bone marrow cells (AML)

Integrated Biomarker Strategy

Supported by compelling preliminary clinical data from a Phase 1b/2 trial showing a ten-fold improvement in ORR compared to SOC

Preclinical data support:• MOA of synthetic lethality between

KRAS mutant mCRC and PLK1 inhibition

• Synergy with irinotecan and 5-FU

First Indication: 2nd line treatment in patients who have failed 1st line treatment with FOLFOX with/without bevacizumab

FDA Fast Track Designation

Strong Lead Program in KRAS-mutated mCRC

Onvansertib overcomes the shortcomings of prior PLK inhibitors:

• Highly selective for PLK1• Orally administered• 24-hour half-life • Flexible dose and schedule

Specifically targets a known mechanism of cell division that is required for tumor cell viability

Preliminary clinical data demonstrate the safety, tolerability and efficacy of onvansertib in combination with SOC across multiple indications

3rd Generation, 1st-in-class, Oral PLK1 Inhibitor

Thank Youfor more information contact: [email protected]

turning the tide on cancer...turning the tide on cancer february 2021 forward-looking statements...

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